Cellular mechanisms for the uptake, transport, digestion, excretion and storage of proteins, lipids and metals in normal tissues and experimental models of disease will be studied, utilizing cytochemical procedures for demonstrating tracer compounds in the light and electron microscope. Enzymatic staining procedures for demonstrating the endoplasmic reticulum, mitochondria, Golfi apparatus, lysosomes and peroxisomes will be employed together with osmiophilic staining for nucleic acids. Although emphasis will be placed on mammalian hepatocytes, arterial smooth muscle cells, neurons, renal epithelium and endocrine organs other cell types from invertebrate and plant tissues will also be studied in the investigation of structural - functional relationships of subcellular organelles. Morphological studies will be coordinated with biochemical analyses of subcellular fractions, secretions and whole tissues. Development of new staining procedures for ultrastructural cytochemistry will be pursued. Major emphasis will be placed upon the application of cytochemical techniques to the analysis of human disease, utilizing biopsy and post-mortem specimens. Efforts will be made to develop diagnostic procedures and to detect underlying mechanisms of metabolic disease.